Diabetes Flashcards
What is a general definition of diabetes?
Chronic hyperglycaemia
Caused by a lack of or diminished efficacy of endogenous insulin
That can cause specific tissue damage over time
Normal ranges for plasma glucose:
Fasting = 3.5-5.6mmol/l
Post prandial = <7.8mmol/l
What is the epidemiology of diabetes?
> 90% have type 2
<10% have type 1
Affects 2% of the British population but costs 5-10% of the UK health budget
More common in south Asian or African/afro-Caribbean ethnicities
T2 increases prevalence with age; onset is accelerated by stress, pregnancy, illness and certain other drugs
T2 is also associated with cardiovascular disease risk factors e.g. HTN, obesity, hyperlipidaemia, decreased HDLs
What is the aetiology of T1 DM?
Genetic component - 30-50% concordance in MZ twins
Also associated with other autoimmune diseases e.g. hypothyroidism
Other potential triggers for T1 = cold weather (greater initial presentation in winter + more common in colder climates); viruses e.g. measles/mumps/Coxackie B/rotavirus
What is the aetiology of T2 DM?
Genetics - play a significant role
Obesity - under activity + overeating (excess triglycerides)
Increases with age
Hx of gestational DM, CV disease or depression
Increased risk if not breast fed until 6m
What are some rare causes of diabetes?
Pancreatic
i) Pancreatectomy
ii) Acute/chronic pancreatitis
iii) Trauma
iv) Malignancy
v) Other destruction of pancreas – CF, haemochromatosis
Drug induced
i) Steroids
ii) Thiazides
iii) Anti HIV
Endocrine
i) Cushing’s
ii) Hyperthyroidism
iii) Acromegaly
Others
i) Congenital formation of insulin receptor antibodies
ii) Glycogen storage disease
What is the pathophysiology of T1DM?
Immunology:
i) T-cell mediated autoimmune disease → destruction of pancreatic beta cells
ii) First islet antibodies appear in blood during first few years of life - wait until trigger for DM then manifest symptoms within a few weeks
Physiology:
i) Lack of insulin → body perceives lack of glucose →
a) ↓ anabolism → hyperglycaemia (fatigue) →glycosuria, polyuria and thirst (polydypsia) → salt + water depletion → ↑HR + ↓BP (→ death)
b) ↑ catabolism → ↑glyconeolysis, gluconeogenesis and lipolysis (wasting + weight loss) → hyperketonaemia → acidosis (↑RR, ↓BP, ↓T) → diabetic ketoacidosis (→death)
c) ↑ secretion of glucagon, cortisol, GH and catecholamines
What is the pathophysiology of T2DM?
Insulin resistance and secretory failure occur for unknown reasons
i) Though patients will have c.50% of beta cells at diagnosis = less extensive than T1
This also helps them avoid DKAs (mostly)
Hyperglycaemic state still present - physiology same as T1
How does T1DM present?
Usually acutely:
Polyuria
Polydipsia
Weight loss
DKA
How does T2DM present?
Less likely to present acutely with DKA
Asymptomatic - may be a coincidental finding on a blood test
Lack of energy, blurred vision
What are some complications that someone with DM may present with?
Staph skin infections Retinopathy
Polyneuropathy Erectile dysfunction
Arterial disease Inflammation of genitals (due to candida infection) Thromboembolism
Hyperosmolar hyperglycaemic state (HHS)
How do you investigate and diagnose DM?
Blood glucose tests:
When fasting: >7mmol/L
Random: >11.1mmol/L (on 2 separate occasions)
Oral glucose tolerance test
i) Overnight fast → 75g glucose drink → bloods 2hrs later → >11.1mmol/L = diabetes
Haemoglobin A1C test (HB1AC) - measures average blood glucose over past 2-3 months by examining how much glucose is bound to RBCs - >6.5%/48mmol/mol
Need 2x symptoms + 1 abnormal test for Dx
In young adults - consider LADA- GAD/c peptide/ islet cell antibodies
How do you manage T1DM?
Insulin + dietary modification
i) Different injections – short acting, long acting etc
What are some different types of insulin and their characteristics?
Human insulin vs. human insulin analogues (vs animal insulin) - both produced using recombinant DNA but the analogues have been modified to add desired characteristics e.g. extended duration
Soluble/short acting insulin: - SC - 15-30mins before meals - onset 30-60mins, peaking at 1-4hrs - duration of c.9hrs
- IV - onset instantaneous - short half life of a few mins (used in DKA)
Rapid acting e.g. Humalog: SC - onset 15mins - lasts 2-5hrs - ideally given just before meals for best control (not after - may hypo)
Intermediate acting e.g. Humalin (NPH or isophane insulins - modified with protamine):
SC - onset 1-2hrs - max effect 3-12hrs - duration 11-24hrs; usually given at bedtime; are cloudy and must be mixed well before injecting
Long acting e.g. Levemir, Lantus: SC - OD - mimic endogenous basal secretion of insulin, lasting up to 36hrs - achieve steady state after 2-4 days = constant low level coverage; usually given at bedtime
Combination preparations e.g. Humulin 70/30 (70units intermediate + 30units short acting):
- Usually short or rapid acting + intermediate, given SC just before a meal (BD/TDS), never at bedtime
Biphasic analogue mixtures e.g. Humalog mix25, Novomix 30:
- Engineered to give a short peak for immediate consumption of food (15 mins after dosing) and a long, broader peak over the next 12-18hrs; never given at bedtime
What is hypoglycaemia?
Common side effect of mistiming insulin doses (or not enough food, activity, drinking alcohol = delayed hypo - liver cant release stored glucose)
Presents with:
Autonomic - irritable, hungry, nausea, anxious, sweaty, palpitations, pallor
Neuroglycopaenic - dizzy, confusion, tiredness, headache, visual or hearing problems, poor concentration, odd behaviour, LOC, convulsions
Blood glucose (BG/BM) of <4mmol
What is a Diabetic Ketoacidosis/DKA?
Metabolic acidosis + hyperglycaemia + ketonuria
i) During normal feeding/physiology – ketone body production at a minimum
ii) Carbohydrate shortage causes increased production of ketones by liver from the acetyl-CoA from fatty acid oxidation
iii) Limited supply of glucose due to depleted circulating insulin and an increase in fatty acid oxidation due to increased circulating glucagon
The resulting excess ketone body production is more than the tissues can oxidise them and as ketone bodies are acidic (pKa 3.5), blood pH lowers
What are the symptoms of a DKA?
Water: Polyuria, thirst; dehydration
GI: Nausea/vomiting; abdominal pain
Limbs: Leg cramps; peripheral cyanosis/cold extremities
Heart: Hypotension; tachycardia
Lungs: SOB; Kussamaul breathing (deep + laboured)
Face: Blurred vision’ acetone smell on breath
Consciousness: Weight loss, weakness; confusion, drowsiness, coma
How do you investigate a DKA?
Obs/examination
i) GCS <12
ii) Temp – low (or high if DKA secondary to infection)
iii) Systolic BP <90
iv) HR >100 or <60
Bloods
i) Ketones - >6mmol/L
ABG
i) O2 sats (not on gas) <92%
ii) Bicarb <5mmol/L
iii) pH <7.3; severe if <7.1
iv) hypokalaemia <3.5
v) Raised anion gap
What are some triggers for DKA?
Infection - flu, UTI etc
Not following a treatment plan
Injury or surgery
Taking corticosteroids and some other medications
Binge drinking, taking drugs
Pregnancy, having your period
No identifiable trigger
How do you manage DKA?
ABC i) ?intubate ii) Cannulate iii) Give O2 iv) Catheter FOLLOW TRUST PROTOCOLS
Insulin
i) Weight based dose given on a Fixed Rate Intravenous Insulin (???)
Fluids
i) 0.9% NaCl maintenance + rehydration (/48hrs) +/- bolus
Maintenance = special formulas (dont need to know yet)
Rehydration can be worked out empirically from the ABG:
5% dehydrated = +50ml/kg
10% dehydrated = +100ml/kg
Bolus = 10ml/kg - less than in non DKA because at large volume and high rates, there is an increased risk of cerebral oedema in this group (same reason why rehydrated /48hrs not 24)
Monitor and add K as appropriate - K is taken up with insulin – no insulin taken into cells = raised extracellular K
When glucose is <14mmol/L:
- Give 10% glucose 500ml at 50ml/hr +/- KCl depending on levels
What do you do if too much K+ is given?
If plasma-potassium concentration above 6.5 mmol/litre there are identifiable ECG changes:
Cardioprotect - Calcium gluconate IV (slow)
Adult:
10–20 mL, calcium gluconate 10% should be administered, dose titrated and adjusted to ECG improvement
(also given in acute hypocalcaemia)
What monitoring is needed for DKA?
Standard regular obs
Use blood ketones (not urine) - resolved when <0.6mmol/L and venous pH >7.3
Can also monitor bicarb - but only for first 6hrs as efficacy decreases when IV-ing saline
What is a hyperosmolar hyperglycaemic state (HHS)?
High blood sugars (>30mmol/L) → severe dehydration → increase in blood osmolarity → coma, death
Different from DKA:
Metabolic acidosis is absent or mild
Delirium is more common
Treatment:
i) Correct dehydration with IV fluids
ii) Reduce blood sugar with insulin
What are sick day rules for DM?
Guidelines given by diabetes care team advising what to do with insulin and monitoring etc during a period of illness that does not require admission to hospital
Baseline insulin doses may need adjusting
Glucose monitoring and results recorded increased in frequency - every 3-4hrs, sometimes every 1-2 - these results will then also affect how insulin doses are titrated subsequently
Consider ketone monitoring (blood or urine) - every 3-4hrs, sometimes every 1-2, including through the night; urine ketones greater than 2+ or blood ketones >3mmol/L then person should contact GP or diabetes care team ASAP (as we want to avoid full blown DKA)
Maintain normal eating pattern as close as possible even when appetite reduced; meals can be replaced with carbohydrate rich drinks e.g. juices, sugary drinks, milk etc
3L/5pints of fluid should be drunk; if vomiting or diarrhoea persistent then medical advice should be sought as IV fluids may be needed
When recovered - should continue to monitor BG carefully until normalises
What are macrovascular complications of DM?
Atherosclerosis
i) Stroke
ii) MI
iii) Gangrene → amputation
Also - infection might not look like infection in an ischemic foot as insufficient inflammatory markers are flowing to the area
What is a Charcot foot? How is it investigated and managed?
Acutely:
- A painful red swollen foot in a patient with diabetic neuropathy
- Deformity e.g. ‘rockerbottom feet’
- Loss of function
- Can be painful but surprisingly little/absent - especially given the extent of joint destruction
Investigation:
- Neurovascular assessment of the foot and ankle
- HbA1C testing
- Plain 2 view XR = evidence of bony deformity +/- osteomyelitis (e.g. periosteal reaction)
- MRI (more sensitive for soft tissue or early stage osteomyelitis)
Management:
- Education re. joint damage and DM control
- Immobilisation - with a cast, for 3-6/12 with repeated XR
- Possible use of bisphosphonates
- Surgery - for severe/unstable deformity that if untreated will result in amputation
- Follow up podiatry with special orthotics for life
Healing process takes c.1-2yrs
- Prevent trauma, note temperature changes, check feet daily etc
Manage any complications:
- Fractures, neuropathic ulcers +/- infection/osteomyelitis; amputation
What is diabetic retinopathy?
i) Thickening of basement membrane and increased permeability of retinal arteries → occlusion, aneurysm formation, increased exudates
Blindness is common
What is diabetic nephropathy?
Glomerular damage
Ischemia of afferent/efferent arterioles
Ascending infection
i) Diabetic immunity often compromised – more susceptible to UTIs
Renal hypertrophy
Albuminurea – first detectable marker of diabetic nephropathy
What is diabetic neuropathy?
Unsure aetiology (?)
Types:
i) Symmetrical mainly sensory = stocking and glove disruption
ii) Acute painful = shins, worse at night
iii) Mononeuropathy and mononeuritis multiplex = CN3+6 and carpal tunnel
iv) Diabetic amyotrophy = progressive wasting of muscle tissue
v) Autonomic neuropathy = CV and bladder problems, ED
What is the pathophysiology behind many of the complications?
Related to the duration and degree of hyperglycaemia – good control = fewer complications
Glycation = addition of a sugar to a lipid through non-enzymatic means, leads to the accumulation of AGE’s (advanced glycation end-product) which are implicated in cell damage and inflammation
i) Excess sugar means more AGE’s and greater negative effects
Cells of retina, kidney and nerves do not require insulin for glucose uptake
i) Excess glucose enters cells (excess glycation etc)
Polyol pathway = excess glucose not put into the TCA cycle will be converted into sorbitol → fructose
i) These cannot exit cells so draw water and other ions in down electrochemical gradients → affects cell functioning
ii) Also produces ROS → direct cell damage Microvascular damage
i) Narrowing of vessels → reduction in nutrients and oxygen
ii) Accelerated by release of excess growth factors (VEGF) → more damage through over proliferation
How is T2DM managed?
First line = Diet + Exercise - can reverse a pre-diabetic state in this way
Potential for:
i) Metformin
ii) Sulfonylurea
iii) ‘Glitazones’
iv) Insulin
What is prediabetes?
A state of impaired glycaemic control
Categorised by:
Fasting glu = <7.0mmol/l
Post OGT 7.8-11.0mmol/l
HbA1c = 5.7-6.4%
Need more stuff on drugs and side effects
Metformin SE: N+V+D, stomach cramps, loss of appetite
What monitoring in DM is required?
Blood glucose
- Self monitoring via finger prick test for those taking insulin
- e.g. 4x per day (before each meal and once before bed, but depends on regimen and personal factors)
- Increase monitoring during times of illness and watch for hyperglycaemia
HbA1C – targets are variable:
- e.g. 6.5%/48mmol for those on monotherapy with metformin, but increases slightly if on dual or triple therapy
Blood ketones
- Home blood monitor (NOT URINE, as less sensitive)
BP:
- At least once a year
- Aim for 135/85
Weight:
- Kept low/reduced
- Reinforce dietary control
Eyes:
- At least once yearly checks for diabetic retinopathy
Kidneys:
- At least once yearly U+Es for albumin:creatinine and eGFR
Feet:
- At least once yearly podiatry review by specialist service
Medication:
- Understanding, adherence, side effects etc
What other professionals are involved in DM management?
Dieticians – carb counting
Endocrinologists – long term management
Diabetes specialist nurses – how to insulin, how to self-monitor, hypo/hyper management
Podiatrists – foot care
Ophthalmologists - eye care
More precisely, what are patterns of inheritance for T1DM?
If X has DM: Mother - 2% (though in mothers that develop DM before age 8 - same transmission risk as fathers) Father - 8% Both parents - 10% Sibling - 10% DZ twin - 15% MZ twin - 40%
Specific genetics - c.20 known associated e.g. HLADR3, HLADR4
More precisely, what are some patterns of inheritance for T2DM?
If either mother or father has T2 then risk increases 15%
If both have T2 then risk increases by 75%
MZ twins - 10%
DZ twins - 90%
Thus more heritable than T1, though still not entirely genetically determined
What is the pathophysiology of T1DM initial presentation?
1) Insulin deficiency + glucagon excess
2a) increased blood ketones - vomiting, acidosis, osmotic diuresis
2b) increased blood glucose - osmotic diuresis
3) fluid and electrolyte depletion - cellular dysfunction, shock, cerebral oedema
How do you manage a mild hypo?
Check blood glucose to confirm symptom profile
If conscious and patient able to swallow:
3-5 glucose tablets; 100-200mls fizzy drink/juice
Wait 10 mins - if no response - repeat
F/U with longer acting carb e.g. bread or biscuit
Check BG in 15mins
How do you manage a moderate hypo?
As for mild if possible, if too unwell to cooperate:
0.5-1 tube of glucogel
Wait 10 mins - if no improvement repeat
F/U with longer acting carb, check BG in 15mins
How do you treat a severe hypo?
At this point patient has a reduced level of consciousness +/- fitting:
- do not attempt give anything PO
With venous access:
- 10% glucose with giving set, 50ml boluses
Without IV access
- Glucagon - SC or IM injections
- If <5yrs = 0.5mg
- If >5yrs = 1mg
Wait 10mins
When conscious - follow mild regimen
What is hypo unawareness?
When people are frequently unable to notice when they are hypoing - puts them at risk of severe hypos + being in risky situations to hypo e.g. driving, crossing roads, cooking
Common in people with T1 who have had it for a number of years; also common if have hypo’d recently within the last 2days; stress, depression and alcohol
Also associated with certain medications e.g. beta blockers
Managed with education and mindfulness; if frequent, may also be asked to increase window of glycaemic control - elevating target BG range (poss by changing how one uses insulin) prevent frequently dropping too low
What is reactive/rebound hypoglycaemia?
Is postprandial hypoglycaemia - low blood sugar that occurs after a meal, usually within 4hrs of eating
Cause for most is unknown - may depend on types of food or individual physiology/gut motility; also alcohol, surgeries e.g. for an ulcer, inherited metabolic disorders etc.
Medical evaluation required to see if symptoms definitely reactive hypos; any known underlying cause corrected; ensuring you eat a balanced diet - all food groups, avoid sugary and processed carbohydrates e.g. white bread/pasta - esp on an empty stomach; eat food when you drink alcohol; snacking; insulin dose may need readjusting
What is the Somogyi phenomenon?
Post hypoglycaemic hyperglycaemia
Can be acute or chronic
May be the result of high blood sugar in the morning due to excess insulin at night (too much insulin may make diabetes management unstable)
Possible mechanism: prolonged hypo - physiological stress - glucagon + cortisol + adrenaline release - temporary insulin resistance - hyperglycaemia
Rigorous BG monitoring including at night will help understanding - may need to readjust night doses
What is the Dawn phenomenon?
Different to - though often confused with - Somogyi rebound
Early morning increase in blood glucose occurring between 8-10 hours of sleep secondary to cortisol/adrenaline/glucagon release and subsequent hyperglycaemia (so same mechanism but this one is sleep related whereas Somogyi doesn’t have to be sleep related)
What is the prognosis for individuals with diabetes?
Life expectancy reduced by 23 years
DKA - 10x bigger killer than hypos
30-40% develop microalbuminaemia
25% require laser surgery for retinopathy
Complications are worse for paediatric T2
25% of patients will have an amputation in their lifetime
How do you manage exercise and hypos?
Prevent hypo during exercise:
- reduce insulin with meal before exercise = lower insulin conc. during and higher starting BG, less of a drop during (though hyper or delayed onset hypo may still occur later)
- high intensity exercise burst - 10s intermittently throughout session or to top/tail= increase in adrenaline, raised glucose during and after exercise (may still late onset hypo)
Post exercise - body is more sensitive to insulin (very sensitive within first 2hrs, waning over 48+hrs) - so increase potency of exogenous insulin and subsequent greater glu uptake
Prevent hypo after exercise:
- eat properly after
- reduce insulin with meal after exercise = less insulin during ‘hot spot’ of insulin sensitivity, stable BG for c.8hrs (may be hyper or delayed hypo)
- reduce basal insulin and insulin before and after exercise = less insulin to compensate for increased sensitivity, normal glucose during sleep without excessive carb intake and more stable glucose next day (working out reduction dose may require trial and error)
What are the rules for driving and hypos?
Need to have a BG of above 5 to drive - mornings can be hard sometimes - need to make sure you eat breakfast
If hypo when driving - have to stop and wait 45 mins + BG of over 5 before they can drive again
more cards to update/add
t’s worthwhile thinking of the average patient who is taking metformin for T2DM, you can titrate up metformin and encourage lifestyle changes to aim for a HbA1c of 48 mmol/mol (6.5%), but should only add a second drug if the HbA1c rises to 58 mmol/mol (7.5%)
Dietary advice
encourage high fibre, low glycaemic index sources of carbohydrates
include low-fat dairy products and oily fish
control the intake of foods containing saturated fats and trans fatty acids
limited substitution of sucrose-containing foods for other carbohydrates is allowable, but care should be taken to avoid excess energy intake
discourage the use of foods marketed specifically at people with diabetes
initial target weight loss in an overweight person is 5-10%
HbA1c targets
This is an area which has changed in 2015
individual targets should be agreed with patients to encourage motivation
HbA1c should be checked every 3-6 months until stable, then 6 monthly
NICE encourage us to consider relaxing targets on ‘a case-by-case basis, with particular consideration for people who are older or frail, for adults with type 2 diabetes’
in 2015 the guidelines changed so HbA1c targets are now dependent on treatment:
Lifestyle or single drug treatment
Management of T2DM HbA1c target
Lifestyle 48 mmol/mol (6.5%)
Lifestyle + metformin 48 mmol/mol (6.5%)
Includes any drug which may cause hypoglycaemia (e.g. lifestyle + sulfonylurea) 53 mmol/mol (7.0%)
Practical examples
a patient is newly diagnosed with HbA1c and wants to try lifestyle treatment first. You agree a target of 48 mmol/mol (6.5%)
you review a patient 6 months after starting metformin. His HbA1c is 51 mmol/mol (6.8%). You increase his metformin from 500mg bd to 500mg tds and reinforce lifestyle factors
Patient already on treatment
Management of T2DM HbA1c target
Already on one drug, but HbA1c has risen to 58 mmol/mol (7.5%) 53 mmol/mol (7.0%)
Drug treatment
The 2015 NICE guidelines introduced some changes into the management of type 2 diabetes. There are essentially two pathways, one for patients who can tolerate metformin, and one for those who can’t: SEE DIAGRAMS
Tolerates metformin:
metformin is still first-line and should be offered if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions
if the HbA1c has risen to 58 mmol/mol (7.5%) then a second drug should be added from the following list:
sulfonylurea
gliptin
pioglitazone
SGLT-2 inhibitor
if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then triple therapy with one of the following combinations should be offered:
metformin + gliptin + sulfonylurea
metformin + pioglitazone + sulfonylurea
metformin + sulfonylurea + SGLT-2 inhibitor
metformin + pioglitazone + SGLT-2 inhibitor
OR insulin therapy should be considered
Criteria for glucagon-like peptide1 (GLP1) mimetic (e.g. exenatide)
if triple therapy is not effective, not tolerated or contraindicated then NICE advise that we consider combination therapy with metformin, a sulfonylurea and a glucagonlike peptide1 (GLP1) mimetic if:
BMI >= 35 kg/m² and specific psychological or other medical problems associated with obesity or
BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or
weight loss would benefit other significant obesity-related comorbidities
only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months
Practical examples
you review an established type 2 diabetic on maximum dose metformin. Her HbA1c is 55 mmol/mol (7.2%). You do not add another drug as she has not reached the threshold of 58 mmol/mol (7.5%)
a type 2 diabetic is found to have an HbA1c of 62 mmol/mol (7.8%) at annual review. They are currently on maximum dose metformin. You elect to add a sulfonylurea
Cannot tolerate metformin or contraindicated
if the HbA1c rises to 48 mmol/mol (6.5%) on lifestyle interventions, consider one of the following:
sulfonylurea
gliptin
pioglitazone
if the HbA1c has risen to 58 mmol/mol (7.5%) then a one of the following combinations should be used:
gliptin + pioglitazone
gliptin + sulfonylurea
pioglitazone + sulfonylurea
if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then consider insulin therapy
Starting insulin
metformin should be continued. In terms of other drugs NICE advice: ‘Review the continued need for other blood glucose-lowering therapies’
NICE recommend starting with human NPH insulin (isophane, intermediate-acting) taken at bed-time or twice daily according to need
Risk factor modification
Hypertension
blood pressure targets are the same as for patients without type 2 diabetes (see table below)
ACE inhibitors or angiotensin II receptor blockers (ARB) are first-line
an ARB is preferred if the patient has a black African or African–Caribbean family origin
Clinic BP ABPM / HBPM
Age < 80 years 140/90 mmHg 135/85 mmHg
Age > 80 years 150/90 mmHg 145/85 mmHg
Antiplatelets
should not be offered unless a patient has existing cardiovascular disease
Lipids
following the 2014 NICE lipid modification guidelines only patients with a 10-year cardiovascular risk > 10% (using QRISK2) should be offered a statin. The first-line statin of choice is atorvastatin 20mg on
How do you manage hypos from sulphonylurea’s (gliclazide, tolbutamide)?
Drugs increase insulin release from islet cells so there is potential for hypos
Hypos may last 24-48hrs due to drug half life
10% glucose infusions may be required continuously during this time - 100mls/hr - after the initial period of unconsciousness is treated
If initial BG <1.3mmol/L - omit further doses until diabetes team R/V
If initial BG 3-3.9mmol/L and not explained by a missed meal - reduce usual dose by 50%
What are some typical regimens of insulin dosing?
Basal-bolus:
- Quick acting insulin before meals + 1-2 medium/long acting insulins daily
Twice daily:
- Insulin mixtures BD; often with metformin in T2DM
Once daily:
- T2DM - Medium or long -acting insulin at bedtime together with oral hypoglycaemic agents
What are the names, mechanisms and side effects of the drugs used in T2DM?
Metformin: (500mg OD with breakfast)
- Decreases gluconeogenesis and increases peripheral utilisation of glucose; since it acts only in the presence of endogenous insulin it is effective only if there are some residual functioning pancreatic islet cells
- SE: abdo discomfort, N+V; lactic acidosis, hepatitis; safe in pregnancy; avoid if eGFR <30; U+E annually
Sulfonylureas:
- e.g. gliclazide
- Increase insulin secretion
- SE: hypoglycaemia, GI discomfort; agranulocytosis; avoid in pregnancy
Gliptins:
- e.g. lina’gliptin’
- (dipeptidylpeptidase-4-inhibitors)
- Increase insulin secretion and lower glucagon secretion
Pioglitazone:
- (a thiazolidinedione)
- Reduces peripheral insulin resistance
- Several long term risks e.g. heart failure (CI) bladder Ca (CI)
- SE: bone #, weight increase, visual impairment; avoid in pregnancy
SGLT-2 inhibitors:
- e.g. Canagli’flozin’
- Reversibly inhibits Na-Glu transporter in PCT, reducing glucose reabsorption/increasing excretion
- SE: UTI, DKA, hypoglycaemia, fornier’s gangrene (genital/perianal nec fasc…)
Glucagon-like peptide-1 receptor agonists:
- e.g. Liraglu’tide’
- Binds to this receptor - stimulating insulin secretion, suppressing glucagon secretion and slowing gastric emptying
What is a typical escalation pathway for management in T2DM?
1) Diet/lifestyle:
- Low sugary foods, low fatty foods
- Increase fibre intake, increase low fat dairy and oily fish
- Aim to lose 5-10% of weight if overweight
2) Add metformin
3) Add one of: sulfonylurea OR pioglitazone OR gliptin OR SGLT-2 inhibitor
4) Add an additional one off the list
5) Metformin + sulfonylurea + GLP-1 mimic OR metformin + insulin regimen (e.g. NPH)
